IgA nephropathy (IgAN), also known as Berger disease, is the most common cause of chronic glomerulonephritis and leads to end stage kidney failure in about 25% of cases. Twenty to forty percent of IgAN patients receiving kidney transplants suffer disease recurrence within 5 years of transplant. The onset of IgAN has been associated with upper respiratory tract infections that trigger the mucosal immune system. As a result of hyper-reactivity of the mucosal immune system, B cells produce increased amounts of IgA leading to IgA deposition in kidney glomeruli. IgA deposition leads to glomerular inflammation, resulting in kidney dysfunction, hypertension and slow progression towards kidney failure.
Current treatments for IgAN are aimed at slowing kidney damage and include anti-hypertensives to control blood pressure and steroid treatment to reduce inflammation. Long term dialysis and kidney transplantation are used to treat end stage kidney failure but have a large negative impact on patient quality of life. Currently, no specific treatment is available to correct hyper-active mucosal immune responses or reduce IgA levels.
Research into pathological mechanisms and new treatments for IgAN have been hampered by lack of appropriate animal models. Currently reported mouse models for IgAN include a multigenic outbred model with variable disease progression (ddY mouse), a single gene knockout that affects IgA deposition but not IgA production (uteroglobulin knockout), and a recently reported mouse transgenic for a B cell activating factor (BAFF transgenic). None of these models selectively impact on IgA production and have to date not been widely adopted for IgAN studies.
IgAN is estimated to affect over 60,000 people in the US, and several fold higher incidence of IgAN is reported among Asian populations. IgAN is incurable and the current limited treatment options include management of hypertension and administering non-specific anti-inflammatories in order to delay the need for dialysis or transplantation. No targeted therapies for reducing IgA production are available.